Recently an alternative approach to coronary bypass surgery has been developed. In this non-operative procedure for the improvement of blood flow in patients with coronary artery disease, a catheter with an inflatable balloon at the distal end is inserted into the femoral artery or by brachial cutdown, and is positioned by fluoroscopic control at the appropriate coronary ostium. The process is known as percutaneous transluminal coronary angioplasty (PTCA).
The balloon at the distal end of the catheter has a predetermined maximum diameter. It is filled with a radio opaque dye to permit visualization. Alternatively, the balloon itself may be radio opaque. When the balloon is positioned in the stenosis it is inflated at pressures of from 2 to 11 atmospheres for from 15 to 60 seconds and then deflated. The inflation cycle may be repeated several times to achieve satisfactory results. Normally the luminal diameter of the stenotic vessel increases at least 20% as a result of the treatment.
Angioplasty is not limited to the cardiac vasculature. It has been employed for treatment of single, large atherosclerotic lesions of the renal, iliac and even vertebral arteries. The effect of the expanded balloon is to literally blow open the stenotic zone. Disruption of the wall is marked, including fracture of the calcium in the lesion, tearing of the plaque itself and extravasation of plaque lipid and gruel into the adjacent vessel wall.
The clinical results of angioplasty include endothelial denudation, vascular wall damage, and rupture of the tunica intima vasorum. These injuries have been found to result in many cases in unregulated proliferation of the arterial smooth muscle cells (SMC) with a resulting restenosis. A recent study by Levine et al (The American Journal of Cardiology, Volume 55, pages 673 to 676, March 1985) has shown that restenosis may be expected to occur in as many as 40% of patients that have undergone angioplasty. Often the only practical treatment for restenosis is to repeat the treatment. This may cause further damage to the cell wall and the need for subsequent repetition of the angioplasty procedure.
Heparin is a mucopolysaccharide composed of amino sugar and uronic acid residues which is obtained from beef, porcine, sheep, whale and other mammalian tissue by extraction with a solution of potassium acetate, alkaline ammonium sulfate and the like. Commercial heparin preparations are now widely available from a number of pharmaceutical companies. Heparin preparations are clinically utilized principally as anticoagulants.
Recently it has become known that in addition to its anticoagulant activities, heparin is a powerful inhibitor of arterial smooth muscle proliferation. See, for example, Guyton et al. Circulation Research Volume 46, Number 5 pages 625 to 633, 1980 and Hoover et al. Circulation Research Volume 47, Number 4, pages 578 to 583, 1980.
My co-pending U.S. patent application Ser. No. 364,408, filed Apr. 2, 1982 describes and claims catheters which can be used to insert a solubilizing agent into an artery to dissolve plaque thereby relieving arterial constrictions. The disclosure of this application is incorporated herein by reference.